Lipids Commons^™

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

Attention Deficit Hyperactivity Disorder, Cannabis Use, And The Endocannabinoid System: A Scoping Review, Jennie Ryan, Mitchell Fruchtman, Andrea Sparr-Jaswa, Amy Knehans, Brooke Worster

Department of Medicine Faculty Papers

There is emerging evidence that the endocannabinoid system (ECS) plays a significant role in the pathophysiology of many psychiatric disorders, including attention deficit hyperactivity disorder (ADHD). Increasing evidence suggests that a number of neurobiological correlates between endogenous cannabinoid function and cognitive dysfunction are seen in ADHD, making the ECS a possible target for therapeutic interventions. Cannabis use and cannabis use disorder are more prevalent in individuals with ADHD, compared to the general population, and there is growing popular perception that cannabis is therapeutic for ADHD. However, the relationship between cannabis use and ADHD symptomology is poorly understood. Further understanding of …

Molecular Mechanisms Of Exercise-Stimulated Resolution Of Inflammation And Its Dietary Dependence., Ernesto H. Pena Calderin

Electronic Theses and Dissertations

Diet-induced obesity and adipose tissue (AT) inflammation that ensues sets the stage for systemic metabolic inflammation, disrupted insulin signaling, and eventual type 2 diabetes (T2D) development. At the center of this pathology lies a disruption in endogenous inflammation resolution pathways characterized by an imbalance in lipid mediator production (greater abundance of pro-inflammatory to pro-resolving lipids). Additionally, obese states are characterized by adrenergic deficiency, especially in response to physical activity. Inflammatory processes have been experimentally mitigated by either the pharmacological inhibition of pro-inflammatory signals (i.e., Leukotriene B₄ (LTB₄) and its receptor BLT1, which establishes a potent chemotactic stimulus …

Cholesterol Drugs May Improve Periodontal Disease

New Orleans Dental Association News

Recently, statin treatment applied locally into tissues during both surgical and nonsurgical procedures exhibiting a positive effect on various parameters of periodontal tissue health. When looking at this novel, not yet commonly utilized approach to the local application of statins as an adjunct to periodontal treatment, early studies have shown significant improvement in clinical parameters, such as probing depth and clinical attachment levels. This method of local statin delivery into the tissue shows promise, and should be explored by further research.

Repurposing Clinically Relevant Metabolic Inhibitor Drugs, Difluoromethylornithine (Dfmo) And Orlistat, For Gammaherpesvirus Replication, Lay Paw

Honors Projects

Viruses, including herpesviruses, contribute up to 15% of all human cancers. Murine gammaherpesvirus-68 (MHV-68), a pathogen commonly found in mice, is studied due to its shared homology with several human herpesviruses. Studies done in the Delgado lab via metabolomics analysis show MHV-68 infected cells increase host cell metabolism. Clinically relevant metabolic inhibitor drugs, ɑ-Difluoromethylornithine (DFMO) and Orlistat, respectively block polyamine and lipid production demonstrated a reduction in MHV-68 viral production. Repurposing clinically relevant drugs through the exploration of a different target shows great promise in reducing oncogenic viral titer.

A Revised Synthesis Of The Cationic Lipids Dmri And Mlri, Benjamin A. Kostic

College of Arts & Sciences Senior Theses

Lipid nanoparticles (LNPs) are an increasingly utilized method of intracellular delivery for nucleic acids. The COVID-19 vaccines from Moderna and Pfizer-BioNTech have used LNP technology to combat the recent global SARS-CoV-2 pandemic, saving millions of lives.^1,2 These vaccines consist of a lipid formulation that binds to the anionic phosphate groups of mRNAs and serves as an effective way to transport the nucleic acid across membranes into cells.⁹The mRNA encodes a viral protein. When introduced to cells, the viral protein is produced so that the immune system then can generate an appropriate antibody response.³ However, this approach …

Toxicological Effects And Treatment Of Accidental Ingestion Of Simparica Trio® In Felis Catus: An Investigative Review, Aussia M. Stander

Honors Program: Senior Projects (Public)

Simparica TRIO^®, a canine endectocide manufactured by Zoetis, contains sarolaner, moxidectin, and pyrantel pamoate salt in an orally administered chewable tablet. These compounds are all toxic to both cats and dogs in sufficient amounts. As Simparica TRIO^® rises in popularity among pet owners, Felis catus (felines, cats) in multi-pet households (households with both cats and dogs) are at increased risk of overdosage and toxicosis from accidental ingestion of Simparica TRIO^® due to their smaller weight.

Simparica TRIO^® is not for feline use and little literature exists on the symptoms of and treatment for accidental ingestion …

Impact Of Fads Genotype On Polyunsaturated Fatty Acid Content In Human Milk Extracellular Vesicles: A Genetic Association Study, John J. Miklavcic, Natalie Paterson, Jennifer Hahn-Holbrook, Laura M. Glynn

Food Science Faculty Articles and Research

Background

Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long-chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk.

Methods

Milk was obtained from a cohort of mothers (N = 70) at 2–4 weeks of lactation. SNPs in the FADS gene locus were determined using …

Efficacy And Safety Of Bempedoic Acid In Patients With Hyperlipidemia And Non-Alcoholic Fatty Liver Disease, Sibtain Nisar, Sidra Sohail, Saman Fatima, Muhammad Talha Akhtar, Muhammad Ahmad, Muhammad Waqar Hanif, Masood Khan, Amin Mehmoodi, Jahanzeb Malik

Journal of Community Hospital Internal Medicine Perspectives

Hyperlipidemia and its association with cardiovascular diseases have been significant public health concerns for many decades. Statins have long been the primary therapeutic option for lowering cholesterol levels and reducing cardiovascular mortality. However, a substantial number of patients either do not achieve optimal lipid goals with maximally tolerated statin doses or experience statin intolerance. In recent years, there have been remarkable developments in the field of hyperlipidemia management, leading to the approval of novel hypolipidemic drugs in North America and Europe. This article reviews the clinical development of bempedoic acid, a promising new drug, alone and in combination with ezetimibe, …

Lipid Genetics In Pregnant Women: Maneuvering The Challenges Of Using Degraded Samples, Kylee Meece

Mahurin Honors College Capstone Experience/Thesis Projects

The results of this project will explore a novel approach to lipid metabolism in pregnant women by exploring the relationship between maternal gene expression of genes critical for fat metabolism, protein expression, and maternal and neonatal outcomes. The study will also examine gene expression in lean pregnant women compared to obese pregnant women, shedding light into the adverse pathology of obesity during pregnancy. These findings may uncover a mechanism related to gene-expression that connects unfavorable maternal fat metabolism to inflammation and/or insulin resistance, which may help to uncover future targets for interventions.

The analysis of lipid gene expression requires the …

Managing Stress: A Study Of Stress Response Mechanisms In Mycobacteria, Augusto C. Hunt Serracin

Biology Dissertations - Archive

Mycobacteria encompass many pathogenic species known to cause severe disease in humans. A well-known example is Mycobacterium tuberculosis (Mtb), the causative agent of the lung disease tuberculosis, which kills millions of humans worldwide yearly. Pathogenic mycobacteria like Mtb are challenging to treat because of their innate ability to adapt to environmental stress. Their unique cell physiology and conserved stress responses allow them to combat biological insults, regulate growth, and regulate genes involved in stress; all these responses increase tolerance to antibiotics. The current therapies to treat mycobacterial infections are lengthy and, at times, unsuccessful, partly due to antibiotic tolerance. A …

Elucidating The Role Of Fatty Acid Synthase In Apc-Driven Colorectal Cancer, Courtney O. Kelson

Theses and Dissertations--Toxicology and Cancer Biology

Globally, colorectal cancer (CRC) is the second leading cause of cancer related deaths. Currently, there is a growing incidence rate for individuals aged 20-49 years. Genetic and environmental factors contribute to the risk of this cancer. Early detection of CRC allows for the most effective treatment option in which surgical resection of the primary tumor occurs along with adjuvant chemotherapy. This therapeutic approach contributes to 5-year survival rate of 91%. However, surgical procedures and chemotherapy struggles against metastatic and relapsed CRC resulting in 5-year survival rate of 14%. Inefficacious treatments for relapsed and metastatic diseases emphasizes the need for more …

Revealing The Elusive Mechanism Of Action Of The Lipid Chaperone Fatty Acid Binding Protein 4, Abdul J. Castillo Ibanez

Theses and Dissertations

Fatty acid binding proteins (FABPs) are pivotal in orchestrating lipid trafficking within cells. This dissertation aims to reveal the mechanism of action of adipocyte FABP (FABP4) by meticulously detailing steps for producing uniformly isotopically labeled protein, understanding dynamics and structural changes in aqueous conditions, analyzing protein-membrane interaction with membrane mimicking models, and revealing its membrane-bound state through novel NMR structural elucidation. Chapter 1 provides an overview of FABP4's indispensable role in lipid trafficking, emphasizing its significance in maintaining cellular homeostasis and metabolic regulation. Chapter 2 delves into the optimization of FABP4 protein expression and proposes a high yield recovery and …

Determining The Ideal Concentrations Of Ethanol And Propylene Glycol In Ethosomes For Transdermal Delivery Of Vitamin D3, Rebecca Conner

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Vitamin D₃ is an important chemical in the human body, however, many Americans have low levels of this vitamin. There are plenty of oral supplementations for Vitamin D₃ deficiency, but those of older age and busy schedules may struggle to meet the minimum requirement. A recently developed ethosomal transmembrane delivery system (Touitou, 2000), similar to liposomes but also containing ethanol, allows users to apply a gel dermally and have the desired drug or active ingredient reach the bloodstream faster. However, there is considerable variation in the concentration of ethanol and permeation enhancers used. Using an affordable method to …

Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in …

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan

School of Medicine Faculty Publications

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …

Nanodiscs: A Novel Approach To The Study Of The Methionine Abc Transporter System, Michael T. Winslow

Master's Theses

Membrane transporter proteins play the vital role of moving compounds in and out of the cell and are essential for all living organisms. ATP Binding Cassette (ABC) family transporters function both as importers and exporters in prokaryotes. MetNI is an E. coli Type I ABC transporter responsible for the uptake of methionine into the cytosol from the cell periplasmic space through the cell membrane to maintain intracellular methionine pools. ABC transporters, like other membrane proteins, are most often mechanistically and structurally studied in vitro, solubilized by detergents. However, detergent micelles may affect the conformational changes of membrane proteins relative to …

Development Of Non-Viral Nano-Carriers For Gene Delivery And Covid-19 Vaccines, Zhongyu Li

Dissertations

Gene therapy is one of the most promising medical fields with the potential to effectively advance the treatment of difficult diseases by producing therapeutic proteins or repairing defective gene sequences. However, gene therapy presents severe challenges in delivery including renal clearance, phagocytosis, enzymatic degradation, protein absorption, and cellular internalization barriers, which have been barriers for translation into the clinic. Naked nucleic acids, with their intrinsic negative charge, electrostatically repulse the anionic cell membrane, preventing cellular uptake. Also, they are considered foreign genetic material when introduced into the body and are rapidly cleared by the reticuloendothelial system or degraded by nucleases, …

Photoisomerizable Membrane Active Peptides, Cristina Ventura

Seton Hall University Dissertations and Theses (ETDs)

Membrane active peptides (MAPs) bind and partition into the cell membrane thus causing permeabilization. Many α-helical membrane active peptides contain central proline residues that distinguish the hydrophobic and hydrophilic faces of the helix. The proline induces a bend that produces a helix-hinge-helix motif. Mutation of these proline residues has a significant effect on the activity of the MAP. Azobenzene is a photoisomerizable molecule that switches from its trans to cis isomer upon excitation with ultraviolet (UV) light and from its cis to trans isomer upon excitation with visible light (VL). In this work it is hypothesized that the hinge function …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …